Peptoids, comprised of poly N-substituted glycines, are an attractive substitute for peptides as therapeutics because they can confer higher stability and resistance to peptidase enzymes and there are easier to structurally diversify due to the much greater variability of peptoid sub-monomer side chains. Peptoid-peptide hybrids can potentially provide the benefits of peptoids with the self-assembled secondary structure advantages of peptides. Cyclic peptoid-peptide hybrids can adopt a beta-hairpin-like secondary structure. This cyclic beta-hairpin-like design results from the alternation of the peptide-peptoid sub-units in two antiparallel beta-strands.
Peptides stabilized by cross linking between the amino acid side chains, referred to herein as “stapled peptides,” have become an important tool in the development of protein-protein interaction inhibitors. Stapled peptides have improved cell penetration, enhanced specificity and stability, low cost of manufacturing, and shorter time duration from concept to drug development. However, stapled peptides do not provide various benefits afforded by peptoids and peptoid-peptide hybrids, such as easy diversification of the side chains and easier placement of side chains that can be stapled together to stabilize a preferred structure.